Is CCM2 p.Arg389= (c.1167G>A) pathogenic?

CCM2 p.Arg389= (c.1167G>A) is classified Likely benign in CCM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with CCM2 p.Arg389= (c.1167G>A)?

CCM2 p.Arg389= (c.1167G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CCM2 p.Arg389= (c.1167G>A) in the general population?

CCM2 p.Arg389= (c.1167G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

CCM2 p.Arg389=

c.1167G>A · rs1784216271 · VCV2449558

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.51	GERP -3.4, phastCons 0.005
Overall
CADD	2.237	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,056 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,461,024 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,056
European (non-Finnish)	0.000254%	393,345

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CCM2
Protein: p.Arg389=
Coding: c.1167G>A
MANE Select: NM_031443
dbSNP: rs1784216271
Type: single nucleotide variant
Location: chr7:45075889 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.48 · 8 PDB

Full CCM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCM2 p.Arg389Trp Uncertain significance ★ ⚠ same residue
CCM2 p.Ala186Thr Uncertain significance ★★ ⚠ same condition
CCM2 p.Arg326His Uncertain significance ★★ ⚠ same condition
CCM2 p.Arg423Pro Uncertain significance ★★ ⚠ same condition
CCM2 p.Gln441Arg Uncertain significance ★★ ⚠ same condition
CCM2 p.Ile131Asn Uncertain significance ★★ ⚠ same condition
CCM2 p.Pro102Leu Uncertain significance ★★ ⚠ same condition
CCM2 p.Val374Met Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ccm2-p-arg389 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown